Oritavancin

What is Oritavancin?

• Oritavancin (ORBACTIV) is a lipoglycopeptide antibacterial drug used for the treatment of serious Gram-positive bacterial infections.

What are the uses of this medicine?

• This medicine is used for the treatment of adult patients with acute bacterial skin and skin structure infections (ABSSSI) caused by susceptible isolates of the following Gram-positive microorganisms:

Staphylococcus aureus (including methicillin-susceptible and methicillin-resistant isolates), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus anginosus group (includes S. anginosus, S. intermedius, and S. constellatus), and Enterococcus faecalis (vancomycin-susceptible isolates only).

How does this medicine work?

Oritavancin has three mechanisms of action: (i) inhibition of the transglycosylation (polymerization) step of cell wall biosynthesis by binding to the stem peptide of peptidoglycan precursors; (ii) inhibition of the transpeptidation (crosslinking) step of cell wall biosynthesis by binding to the peptide bridging segments of the cell wall; and (iii) disruption of bacterial membrane integrity, leading to depolarization, permeabilization, and cell death. These multiple mechanisms contribute to the concentration-dependent bactericidal activity of oritavancin.

Who Should Not Use this medicine ?

This medicine cannot be used in patients with:

• known hypersensitivity to oritavancin products
• Use of intravenous unfractionated heparin sodium is contraindicated for 120 hours (5 days) after ORBACTIV administration

What drug interactions can this medicine cause?

• Avoid administering ORBACTIV concomitantly with drugs that are predominantly metabolized by one of the affected CYP450 enzymes. Patients should be closely monitored for signs of toxicity or lack of efficacy if they have been given ORBACTIV while on a potentially affected compound (e.g. patients should be monitored for bleeding if concomitantly receiving ORBACTIV and warfarin).
• ORBACTIV may artificially prolong certain laboratory coagulation tests by binding to and preventing the action of the phospholipid reagents which activate coagulation in commonly used laboratory coagulation tests .
• Positive IAT/DAT were noted with administration of oritavancin products, including ORBACTIV, in studies with healthy volunteers and patients with ABSSSI.

Is this medicine FDA approved?

• This medicine is approved in the year 2014.

How should this medicine be used?

• There are two oritavancin products (ORBACTIV and KIMYRSA™, another oritavancin product) that have differences in dose strength, duration of infusion and preparation instructions, including reconstitution and dilution instructions and compatible diluents.

Recommended Dosage:

• The recommended dosage of ORBACTIV is 1,200 mg administered as a single dose by intravenous infusion over 3 hours in patients 18 years and older.

Administration

• ORBACTIV is intended for intravenous infusion, only after reconstitution and dilution.
• Three ORBACTIV 400 mg vials need to be reconstituted and diluted to prepare a single 1,200 mg intravenous dose.

Reconstitution:

• Aseptic technique should be used to reconstitute three ORBACTIV 400 mg vials.
• Add 40 mL of sterile water for injection (WFI) to reconstitute each vial to provide a 10 mg/mL solution per vial.
• For each vial, gently swirl the contents to avoid foaming and ensure that all ORBACTIV powder is completely dissolved to form a reconstituted solution.
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Each reconstituted vial should appear to be a clear, colorless to pale yellow solution, free of visible particles.

Dilution:

• Use ONLY 5% dextrose in sterile water (D5W) for dilution to prepare the final intravenous solution for infusion. Do NOT use Normal Saline for dilution as it is incompatible with ORBACTIV and may cause precipitation of the drug. Since no preservative or bacteriostatic agent is present in ORBACTIV,
• aseptic technique must be used in preparing the final intravenous solution as follows:
• Withdraw and discard 120 mL from a 1000 mL intravenous bag of D5W.
• Withdraw 40 mL from each of the three reconstituted vials of ORBACTIV and add to D5W intravenous bag to bring the bag volume to 1000 mL. This yields a concentration of 1.2 mg/mL.
• Discard any unused portion of the reconstituted solution remaining in each vial.

Storage and Use of Intravenous Solution:

• Diluted intravenous solution in an infusion bag should be used within 6 hours when stored at room temperature, or used within 12 hours when refrigerated at 2 to 8°C (36 to 46°F). The combined storage time (reconstituted solution in the vial and diluted solution in the bag) and 3 hour infusion time should not exceed 6 hours at room temperature or 12 hours if refrigerated.
• ORBACTIV is administered intravenously. ORBACTIV should only be diluted in D5W. Do NOT use normal saline for dilution as it is incompatible with ORBACTIV and may cause precipitation of the drug.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As injection: 400 mg of lyophilized powder in a single-dose vial for reconstitution.

This medicine is available in fallowing brand namesː

• ORBACTIV

What side effects can this medication cause?

The most common side effects of this medicine include:

• headache
• nausea
• vomiting
• limb
• subcutaneous abscesses
• diarrhea

What special precautions should I follow?

• ORBACTIV has been shown to artificially prolong aPTT for up to 120 hours, and may prolong PT and INR for up to 12 hours and ACT for up to 24 hours. For patients who require aPTT monitoring within 120 hours of ORBACTIV dosing, consider a non-phospholipid dependent coagulation test such as a Factor Xa (chromogenic) assay or an alternative anticoagulant not requiring aPTT.
• Serious hypersensitivity reactions, including anaphylaxis, have been reported with the use of oritavancin products, including ORBACTIV. Discontinue infusion if signs of acute hypersensitivity occur. Carefully monitor patients with known hypersensitivity to glycopeptides.
• Administer ORBACTIV over 3 hours to minimize infusion. Infusion related reactions have been reported with the glycopeptide class of antimicrobial agents, including oritavancin products (e.g. ORBACTIV). Stopping or slowing the infusion may result in cessation of these reactions.
• Clostridioides difficile-associated diarrhea (CDAD) has been reported for nearly all systemic antibacterial drugs, including ORBACTIV. Evaluate patients if diarrhea occurs.
• ORBACTIV has been shown to artificially prolong prothrombin time (PT) and international normalized ratio (INR) for up to 12 hours, making the monitoring of the anticoagulation effect of warfarin unreliable up to 12 hours after an ORBACTIV dose. Patients should be monitored for bleeding if concomitantly receiving ORBACTIV and warfarin.
• Osteomyelitis may occur. Institute appropriate alternate antibacterial therapy in patients with confirmed or suspected osteomyelitis.

What to do in case of emergency/overdose?

• In the ORBACTIV clinical program there was no incidence of accidental overdose of ORBACTIV.

Management of overdosage:

• Based on an in vitro hemodialysis study, ORBACTIV is unlikely to be removed from blood by hemodialysis. In the event of overdose, supportive measures should be taken.

Can this medicine be used in pregnancy?

• There are no available data on ORBACTIV use in pregnant women to evaluate for a drug- associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.

Can this medicine be used in children?

• Safety and effectiveness of ORBACTIV in pediatric patients (younger than 18 years of age) have not been established.

What are the active and inactive ingredients in this medicine?

Active Ingredient:

• ORITAVANCIN

Inactive Ingredients:

• MANNITOL
• PHOSPHORIC ACID

Who manufactures and distributes this medicine?

Marketed By: Melinta Therapeutics, LLC Lincolnshire, IL 60069 USA

What should I know about storage and disposal of this medication?

• ORBACTIV vials should be stored at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).

• Dailymed label info on Oritavancin
• FDA Oritavancin

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